Transformation of Follicular Lymphoma to Plasmablastic Lymphoma With c-<i>myc</i> Gene Rearrangement

Ouansafi, Ihsane; He, Bing; Fraser, Cory R.; Nie, Kun; Mathew, Susan; Bhanji, Rumina; Hoda, Rana S.; Arabadjief, Melissa; Knowles, Daniel M.; Cerutti, Andrea; Orazi, Attilio; Tam, Wayne

doi:10.1309/ajcpwy1sgj9ieaor

Cited by 38 publications

(31 citation statements)

References 30 publications

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“…STAT1 had a low expression level in DN-p38 JB6 Cl41 cells in Table 2 and we already confirmed that STAT1 was the downstream of p38 MAP kinase and regulated JB6 Cl41 cell transformation. Many studies show that myc proto-oncogene mediates cell transformation (Bapat et al, 2010;Figueiredo et al, 2010;Ouansafi et al, 2010;Sablina et al, 2010). Our data showed myc proto-oncogene had low expression level in EGF-stimulated DN-p38 JB6 Cl41 cells and this result indicates that myc proto-oncogene also played a role in EGF-induced JB6 Cl41 cell transformation and it should be the downstream of p38 MAP kinase.…”

Section: U58533supporting

confidence: 49%

Analysis of the role of p38 MAP kinase in epidermal growth factor-induced JB6 Cl41 cell transformation by cDNA array

Cui

et al. 2012

Gene

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Section: U58533supporting

confidence: 49%

Analysis of the role of p38 MAP kinase in epidermal growth factor-induced JB6 Cl41 cell transformation by cDNA array

Cui

et al. 2012

Gene

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“…Secondary PBL transformed from chronic lymphocytic leukemia or FL also frequently harbor MYC translocations. 83,84 All of these observations suggest that MYC aberrations do also play a role in the pathogenesis of aggressive lymphoid neoplasms with terminal B-cell differentiation. This finding is remarkable because most aggressive B-cell lymphomas with MYC rearrangements have a GC phenotype.…”

Section: Dh/th Lymphomamentioning

confidence: 99%

Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification

Ott

Rosenwald

Campo

2013

Blood

214

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MYC is a potent oncogene initially identified as the target of the t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. MYC gene alterations have been identified in other mature B-cell neoplasms that are usually associated with an aggressive clinical behavior. Most of these tumors originate in cells that do not normally express MYC protein. The oncogenic events leading to MYC up-regulation seem to overcome the inhibitory effect of physiological repressors such as BCL6 or BLIMP1.Aggressive lymphomas frequently carry additional oncogenic alterations that cooperate with MYC dysregulation, likely counteracting its proapoptotic function. The development of FISH probes and new reliable antibodies have facilitated the study of MYC gene alterations and protein expression in large series of patients, providing new clinical and biological perspectives regarding MYC dysregulation in aggressive lymphomas. MYC gene alterations in large B-cell lymphomas are frequently associated with BCL2 or BCL6 translocations conferring a very aggressive behavior. Conversely, MYC protein up-regulation may occur in tumors without apparent gene alterations, and its association with BCL2 overexpression also confers a poor prognosis. In this review, we integrate all of this new information and discuss perspectives, challenges, and open questions for the diagnosis and management of patients with MYC-driven aggressive B-cell lymphomas. (Blood. 2013;122(24):3884-3891) Introduction MYC was initially identified as the target oncogene dysregulated by the t(8;14)(q24;q32) translocation in Burkitt lymphoma (BL). MYC rearrangements involving the heavy-and light-chain immunoglobulin (IGL) loci and different non-IG genes were subsequently detected in other lymphoid neoplasms usually associated with very aggressive clinical behavior.1,2 The transforming oncogenic potential of MYC was initially demonstrated in cell lines and transgenic animal models. However, MYC dysregulation alone does not cause lymphoma, 4 and the t(8;14) has been found at very low levels in blood and BM of healthy individuals, 5 indicating that this genetic alteration per se is not sufficient to trigger lymphomagenesis. BL and most lymphomas carrying MYC translocations are among the most proliferative tumors. However, MYC expression has been difficult to identify in the germinal center (GC), the lymphoid cell compartment with the highest proliferative fraction, where most of these tumors originate. Understanding the possible role of MYC in normal lymphoid regulation and particularly the modulation of the GC reaction has been elusive.Recent studies, including basic immunology analyses, new animal models, next-generation sequencing, and clinicopathological observations, are converging to provide a new perspective of the role of MYC in the lymphoid system and the pathogenesis of aggressive lymphomas. In this review, we integrate all of this new information and discuss new perspectives, challenges, and open questions for the diagnosis and management of patients. MYC as a transc...

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“…PBL is associated with rearrangements in the c-MYC gene in more than 40 % of cases [42,43]. Valera and colleagues reported c-MYC rearrangement in 50 % of the cases reviewed and noted that EBV positive patients are more likely to have the c-MYC abnormality and cmyc rearrangement occurs less frequently in EBV negative patients [44].…”

Section: Cytogenetic Analysismentioning

confidence: 99%

Clinicopathologic features of plasmablastic lymphoma: Single-center series of 8 cases from Saudi Arabia

et al. 2015

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Background: Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin's lymphoma. Characterized by its aggressive nature and plasmacytic differentiation, PBL remains a therapeutic and diagnostic challenge; it generally has a poor prognosis with very few long-term survivors and most patients dying within 2 years from initial presentation. PBL has been reported in several other countries; however, there have been no reported cases from Saudi Arabia. Here, we report 8 cases of PBL depicting the clinical presentation, immunocompetency, immunphenotypic characterization, diagnostic challenges and treatment outcome. Methods: The medical records were reviewed for clinical presentation, staging, laboratory data, radiological studies, treatments, and outcomes. A broad immunohistochemical panel consisting of CD45, CD3, CD20, CD79a, Pax5, CD38, CD138, MUM1, EMA, Kappa, Lambda, CD 56, CD30, Bcl-2, Bcl-6, Alk-1, Ki-67, EBV-LMP-1, and HHV8 was performed. Results: The tumors predominantly exhibited immunoblastic/plasmablastic or plasmacytic morphologic features and had a plasma cell-like immunophenotype. All cases were immunoreactive for CD38, CD138 and MUM1 confirming plasma cell differentiation of the tumor cells. CD20 was negative for all cases; whereas CD79a and Pax5 were weakly positive in 2cases. All 8 cases were EBV-LMP-1/EBER-1 negative, and 1 case was HHV8 positive. Similar to previously published studies, PBL in Saudi Arabia is characterized by male predominance (6/8), median age 51.5 years (mean age 46 years), associated with early dissemination, poor response to therapy, and limited survival (average survival time, 6.4 months, median overall survival 5.5 months). However, it does have some unique features. It occurs more commonly in immunocompetent persons (6/8, 75 %), is not associated with EBV infection (0/8), and nodal involvement (either primary or secondary) is common among patients (6/8). In addition, extra-oral sites are more common than oral/nasal cavities (7/8) and the c-myc gene is not common (1/8, 12.5 %).

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Transformation of Follicular Lymphoma to Plasmablastic Lymphoma With c-myc Gene Rearrangement

Cited by 38 publications

References 30 publications

Analysis of the role of p38 MAP kinase in epidermal growth factor-induced JB6 Cl41 cell transformation by cDNA array

Analysis of the role of p38 MAP kinase in epidermal growth factor-induced JB6 Cl41 cell transformation by cDNA array

Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification

Clinicopathologic features of plasmablastic lymphoma: Single-center series of 8 cases from Saudi Arabia

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